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Monthly Archives: October 2012

Michael O’Reilly, PhD

Department of Pediatrics

Laboratory Support Center Awardee

Dr. O’Reilly received a Laboratory Support Center Award in 2007 for his proposal, “Genome profiling of innate-immune privileged lung epithelial cells.” The research funded by this RFA has led to advances in the study of how premature oxygen exposure affects children throughout life. It has also led to the creation of the Perinatal and Pediatric Origins of Disease (PPOD) Program in the Department of Pediatrics. The PPOD Program will be run by Dr. O’Reilly.

Dr. O’Reilly’s involvement with the CTSI began when his research was becoming translational. He says he saw the opportunity to use the CTSI’s resources in order to help move his research forward. At the time the Laboratory Support RFA was announced, Dr. O’Reilly was considering doing microarrays using the Functional Genomics Center. His lab had done one set of microarrays, but they were very expensive. Dr. O’Reilly says using the core facilities with the CTSI’s laboratory support allowed him to complete those studies.

Research Focus: Why do children born prematurely have increased risk for respiratory viral infections?

Dr. O’Reilly’s research is focused on trying to understand why children born prematurely have increased risk for respiratory viral infections. One of the biggest issues of premature birth is that the lung is not ready to breathe the air the child is exposed to when born. When this happens, the child must be given extra oxygen in order to survive. The combination of the room air and the extra oxygen causes the lung to develop abnormally, which renders it unable to deal well with respiratory viruses.

Treating the effects of premature birth is a life-long process. There are repeated doctor visits, hospitalizations, and the complications of dealing with disorders or diseases like asthma or Bronchopulmonary Dysplasia, a chronic form of lung disease frequently seen in preterm infants with very low birth weight. In 2005, the National Heart Lung Blood Institute (NHLBI) estimated the annual financial cost of treating prematurity to be $26.2 billion. $2.5 billion of that total was designated to treating Bronchopulmonary Dysplasia, which requires supplemental oxygen treatment in premature babies. Dr. O’Reilly says these treatments, as well as other therapies like vaccines, are similar to giving eyeglasses to people who have difficulty seeing. “It helps, but it hasn’t really solved the disease – it has just attenuated the disease,” he said.

Click here for a video of Dr. O’Reilly explaining the eyeglasses analogy

In order to develop therapies to improve the long-term health of children born prematurely, Dr. O’Reilly says he first needs to understand why being born prematurely affects the lung’s ability to properly protect against infection. This was the goal of the project funded by the Laboratory Support Center Award.

Dr. O’Reilly’s project focused on identifying genes that were differently expressed in two populations of cells, where one of those populations was depleted in lungs that had been exposed to high levels of oxygen. Dr. O’Reilly says he needed to know what these cells made because it could indicate what was deficient in the lung.

Click here for video of Dr. O’Reilly explaining his CTSI pilot program proposal

In order to determine this, Dr. O’Reilly isolated the two populations of cells and ran gene arrays on each. By looking for the expression of every gene in these cells and comparing them to each other, he found that only 0.5% of all the genes were differently expressed in both populations. Dr. O’Reilly said he targeted a set of these genes and attempted to find relevance in an experimental mouse model that examined how oxygen made the lung more sensitive to infection with respiratory viruses like influenza. He studied two groups of mice: mice born into room air and mice that were given high oxygen at birth. After allowing the mice to grow up, he gave them respiratory viruses. He found that the mice born into room air became sick and then recovered, but the mice who were given high oxygen at birth became sicker than the first group and did not recover as efficiently. After further study, Dr. O’Reilly determined that the depleted cell population was not only missing in the mice exposed to high oxygen, but that those cells actually made an antiviral gene that blocked viral replications.

“So now we had a lung that was deficient in a cell that prevented viruses from replicating in the lung,” Dr. O’Reilly said. “What we wanted to do was take that information and move it forward by restoring and rescuing the phenotype.”

Dr. O’Reilly and a colleague then developed a tool that delivers the depleted gene back into the lung. As a result, it is possible to restore high level expression of this gene, essentially replacing what the cell was supposed to be producing.

“In doing so, now we’ve actually rescued the mice, much like you’d do with a vaccine. The mice don’t get as sick anymore,” Dr. O’Reilly said. “Now we have a new potential candidate to study in children that are born prematurely and we can ask, ‘is this the same gene or is this population of cells deficient? And if it is, can we use these kinds of tools that we’ve started to develop in experimental models to treat children in the future?’”

This study was recently finished and is about to be sent out for peer review.

“We think we really stumbled onto something that’s going to have a lot of translational merit,” Dr. O’Reilly said. “Hopefully, it will help us solve what’s going on with kids that are born prematurely.”

Translational Research: Dialogue across disciplines

Dr. O’Reilly says the next step in his research is to try to understand a spectrum of disorders associated with prematurity and oxygen exposure. It is well known that children born prematurely have deficits in lung and immune function, difficulty dealing with respiratory viruses, and increased risk for asthma. However, recent studies in Australia have shown that children born prematurely have high risk for high blood pressure as well. Other studies show an increased risk for retinopathy, and also neurodevelopmental delay, which often requires children to have extra assistance in the classroom.

Dr. O’Reilly is collaborating with several faculty members in order to gain a better understanding of what causes these disorders. Dr. Deborah Cory-Slechta in Environmental Medicine is studying the cognitive effects of the brain in mice exposed to high oxygen at birth. She has concluded that these mice have deficits in locomotor activity, which suggests that their brains might be wired differently. In addition, Dr. Paige Lawrence in Environmental Medicine has helped Dr. O’Reilly develop the influenza model. Furthermore, Dr. David Dean in Pediatrics and Neonatology has developed a novel method to restore gene expression in the lungs of mice. Dr. O’Reilly is also working with researchers interested in fibrosis because the cells he has identified may play a role in protecting against this scarring disorder.

“Essentially, it’s been able to open up a lot of doors for us by identifying this set of genes in this small population of cells,” he said of the collaborations.

The joint efforts have also led to additional funding. The preliminary data generated from the research supported by the Laboratory Support Center Award led to an individual research grant (R01) from the NIH. The R01 allows the O’Reilly Lab to move forward with the studies on how oxygen affects the aforementioned small population of cells. In addition, Dr. O’Reilly and Dr. Paige Lawrence received a second R01 to study the antiviral properties of this gene (which supports Dr. Lawrence’s interest in studying flu).

“One of the nice things about working at Rochester is that it’s a small enough place to not only go between the CTSI where I can do pilot projects and have interface with using their laboratory support stuff, but I can also walk into the Department of Pediatrics and I can talk to my clinical colleagues.”

Dr. O’Reilly says going from the bench to the bedside keeps him true to form because he can ask if what he is studying will indeed have impact in humans. For instance, his interactions with colleagues in the Department of Environmental Medicine have posed the question of whether children born in major cities with higher levels of urban pollution will be more or less at risk to disorders associated with prematurity. He says he can also walk into a basic science department like Biochemistry and ask researchers studying DNA damage and repair how oxygen affects DNA, if cells respond to damage in DNA because of oxygen, and if that is causing the changes seen in the lung.

“I think it’s an exciting place to be because I can actually go from the bench to the bedside and back again and I can talk to a bunch of different people very easily,” Dr. O’Reilly said. “That’s one of the pluses about staying here in Rochester to do this because you can have the CTSI across the street from basic science.”

Dr. Nina Schor, Chair of the Department of Pediatrics, agrees. She says the CTSI has changed the culture of the University of Rochester Medical Center.

“It really allowed us to dare to think across traditional lines,” Dr. Schor said. “It opened as an institutional policy rather than as an exception to a rule, the dialogue between the clinic and the laboratory. That, to me, really has been a hallmark of the recent advances that we’ve had in medicine. I think every place where we’ve had an advance has come from a dialogue between the researchers and the clinicians.”

Click here for video of Dr. O’Reilly and Dr. Nina Schor explaining the Perinatal and Pediatric Origins of Disease Program

Click here for video of Dr. O’Reilly and Dr. Nina Schor explaining the benefits of working with the CTSI

A Personal Touch: “This may be a reason I’m called to do this – to help my family”

“There’s always a philosophy of why do you do research? I thought about this a lot and we become scientists because we are generally curious people and we want to know how the system works.”

Dr. O’Reilly’s interest in studying prematurity began during his training in the 1980’s. His mentor was interested in surfactant, which is a protein lipid mixture made by the lung. Surfactant allows the lung to open and expand more readily and deliver oxygen more efficiently.

“I still remember being a graduate student when the fellow came running back with the first clinical sample of surfactant that they put into a child who was blue, because they couldn’t get enough oxygen in the lungs,” Dr. O’Reilly said. “It expanded [the child’s] lungs so much, they couldn’t turn the oxygen saturations down fast enough because the child had turned pink so quickly.”

“It saved lots and lots of lives and now we’re dealing with trying to do the follow-up, basically. We saved your life being born prematurely, but now how can we improve the quality of life later on?”

Dr. O’Reilly says the research to which he and thousands of other contributed led to the development of therapies which now serve as standard of care for babies born prematurely: they receive reduced levels of oxygen, milder ventilation, and are treated with surfactant.

“20 years later, I’m a scientist studying how cells respond to oxygen – the same oxygen we worry about because we still have to give oxygen to these preemies – and my son, Thomas, was born prematurely by about seven weeks,” Dr. O’Reilly said.

Thomas was treated in the NICU at Strong Memorial Hospital by Dr. O’Reilly’s colleagues who also study surfactant biology. Fortunately, Thomas did not need high levels of oxygen or excess surfactant.

“I became very intrigued by the concept of what happened 20 years earlier, where I was being trained by somebody interested in surfactant. Now, watching children today being treated with surfactant in the pods around me – around my son, in particular – and I became very interested in what’s going to happen to these children as they grow up, and in particular, what’s going to happen to my son.”

As a result, Dr. O’Reilly then decided to move his research in the direction of neonatal oxygen exposure. His focus is on how oxygen in the early stages of lung development can permanently reprogram how the lung and other organs function late in life.

“I’m excited to actually participate in it because every day I go home and I have to look at my son and I have to say to myself, ‘did I do a good job at work today and how could this help Thomas?’”

Dr. O’Reilly’s second child, Kathryn, was also born prematurely.

“This may be a reason why I’m called to do this – to help my family, but also to help all the other children that we now treat all the time so that they can have as best of a possible life in the future,” Dr. O’Reilly said. “As some of my colleagues say, ‘you’ve spent the past ten years studying oxygen simply to get to where you are now.”

Click here for video of Dr. O’Reilly explaining why he believes that studying oxygen is his calling

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Regis O’Keefe, MD, PhD

Chair, Department of Orthopaedics

Associate Dean for Clinical Affairs

Dr. Regis O’Keefe is the Chair of the Department of Orthopaedics and the Associate Dean for Clinical Affairs at the University of Rochester Medical Center. An orthopaedic oncologist, he earned his medical degree at Harvard Medical School and completed a residency in orthopaedic surgery at the University of Rochester Medical Center. Following his residency, he completed a fellowship in orthopaedic oncology at Massachusetts General Hospital. In order to better understand the diseases he treats, Dr. O’Keefe earned a PhD in biochemistry at URMC while conducting research.

As part of the CTSI Mentoring Program, Dr. O’Keefe has served as a mentor to students in the TL1 Pre-doctoral Training Program and the KL2 Career Development Program. He has had the opportunity to work with four individuals: Matthew Brown (TL1, 2011-2012), Roman Eliseev (KL2, 2010-2012), Evan Katzel (TL1, 2007-2008), and Sirish Kondabalu (TL1, 2010-2011). Dr. O’Keefe says being a mentor is one of the great privileges he has as a scientist.

“Probably the biggest impact you have is the way you can shape programs or work with people that are going to multiply what you do and take what you have thought about or done to much further levels,” he said. “I think that being a mentor has been one of the really exciting things about science and being a scientist.”

As a philosophy and religious studies major at Yale University, Dr. O’Keefe took only the minimum science requirements to enter medical school. He says the world of science opened up to him when he enrolled at Harvard Medical School and saw the personal benefits of taking care of patients with diseases.

“It was very important for me at that time to do something to contribute to the field of medicine,” he said.

Dr. O’Keefe then began doing research with his first mentor, Dr. John Powell, a cardiovascular physiologist at Massachusetts General Hospital. He says this experience in the lab was unique because he was assigned his own project; he knew the work he was doing was significant because it added new information to the field.

“The basic, fundamental thing about the excitement of it and having something that you’re trying to create that’s new and different – that’s what’s been so attractive to me.”

According to Dr. O’Keefe, one of the challenges in becoming successful as a scientist today is that trainees often do not have the opportunity to do hands-on experiments. Now, as he serves as a mentor to young students, he draws on his first, key experience in the lab. Nearly all the work he does is in collaboration with trainees, and he strives to ensure that his students feel an ownership of their projects and the discovery involved with the work. He says this is essential in creating a successful team.

“I’ve found that a mentoring relationship really is a partnership and that you really want to enable the people around you to work as effectively as possible,” he said. “That creates the best science.”

Dr. O’Keefe says the CTSI Mentoring Program has helped him become a better mentor, yet he has received more from his protégés than he’s given.

“They are not initiated into the science, they don’t have all the background that I have, so they come at this in a very fresh way,” he said. “It’s exciting to work with people that have the energy and new vision about the approaches.”

In addition to its benefits at the individual level, Dr. O’Keefe says the CTSI’s Mentoring Program has also created a style of work that influences all URMC research centers and departments, including the Center for Musculoskeletal Research.

“It creates a culture of mentoring,” he said. “Mentors and protégés in a good relationship align their goals and they really enable one another. That culture of collaboration, I think through something like the CTSI, can reach across the institution.”

Click here for a video of Dr. O’Keefe explaining the privileges of being part of a mentoring relationship.

Nancy Needler

Nancy Needler is the Research Subject Advocate for the Clinical and Translational Science Institute. She is an independent resource for study volunteers (subjects), as well as researchers and study coordinators at the University. In her role, she assists investigators with many facets of study management, including the informed consent process and the development of the Data and Safety Monitoring Plan. Needler is also the primary liaison for the ResearchMatch recruitment tool. In the fall of 2011, the University of Rochester CTSI was named the first-quarter recipient of the MatchMaestro Award from ResearchMatch for successfully recruiting more study volunteers than any other institution.

ResearchMatch

ResearchMatch is a secure, free, web-based matching tool which helps connect researchers and prospective study volunteers. This nationwide, volunteer registry is funded by the National Institutes of Health and managed by Vanderbilt University. Under the Clinical and Translational Science Award consortium collaboration, the University of Rochester is one of 67 institutions utilizing ResearchMatch.

ResearchMatch for Volunteers

The ResearchMatch registry is open to volunteers of all ages and health conditions in the United States. Individuals are instructed to self-register by filling in their name, contact information, health conditions, and medications on the ResearchMatch website. Registration only takes about five minutes. Personal information is protected until the volunteer agrees to take part in a research study.

When ResearchMatch matches volunteers with study criteria, the system provides an e-mail link to the researcher, who can then send a secure, IRB-approved recruitment message to prospective participants. If a volunteer agrees to be contacted, ResearchMatch provides the researcher with the individual’s contact information. Volunteers always have the option to decline participation.

MatchMaestro Trophy

In order to recognize the institutions which successfully enroll the highest number of research volunteers each quarter,

Dr. James Dolan and Qinghua Li (Study Coordinator)

Vanderbilt University created the MatchMaestro trophy. The University of Rochester CTSI was named the inaugural winner, enrolling 162 study volunteers from September 15, 2011 to December 31, 2011. The trophy was awarded to the University based heavily on the enrollment of Dr. James Dolan and his team in the Department of Public Health Sciences.

“The trophy is here in Rochester now and we don’t want to lose it,” Needler said. “The point is to keep our researchers and volunteers connected, and ResearchMatch is one of the best ways to do it.”

The University’s success in using ResearchMatch is noteworthy:

# Volunteer Enrollments through RM (9/15/11-12/31/11)

162

# Volunteers Listed on RM who Reside within 50 Miles of UR

692

# Volunteers Contacted

8,888

# Volunteers Responding as Interested

2,026

#Active Researchers

40

# Active Studies

11

“It’s not really about the recognition of the trophy, as pretty as she is,” Needler said. “It’s really about having researchers connect with their volunteers in any recruitment process at all…but we like the trophy!”

To read more about the MatchMaestro Award and the University’s success with ResearchMatch, click here.

Click here for a video of Nancy explaining ResearchMatch and the MatchMaestro Award.

Why Should I Register for ResearchMatch?

Nancy Needler

“Moving research forward, whether it’s a drug, device, biologic, or other types of health research, will help the future treatment of medical conditions.” Needler said.

Researchers need study volunteers to determine if the treatments they investigate are successful. Without volunteers, improving our nation’s healthcare would not be possible.

“If you’re looking to see what you can do to improve medical care – to be involved because [research] is a very exciting place to be right now – then this is a very safe way you can connect to researchers.”

Dr. Daniela Geba is a second-year PhD student in the Translational Biomedical Sciences (TBS) program at the University of Rochester Medical Center. Her journey to Rochester – like the innovative TBS program – is unique.

After earning her medical degree at the University of Medicine and Pharmacy Gr. T. Popa, Iasi, Romania, Dr. Geba relocated to the United States, joining her husband, who was earning his PhD in mathematics at Princeton University. During her first several years in the U.S., Dr. Geba put her career on hold to raise the couple’s two daughters and help make the transition from Romania easier. When her daughters got older, she decided to resume her training and pursue her PhD. She then enrolled in an epidemiology program at the University at Buffalo, and later, in the TBS program at URMC.

Dr. Geba’s research interest is in the broad area of cardiovascular disease, with a focus on diabetes mellitus. She is currently developing a clinical trial which will compare screening strategies for type 2 diabetes.

Translational Biomedical Sciences Program

The Translational Biomedical Sciences program is one of the first of its kind in the nation. This non-traditional PhD program prepares students for careers in academic and clinical settings, emphasizing the adaption of basic biomedical science for clinical practices.

“Described often using the phrase, ‘from bench to bedside,’ translational research is meant to be the process which facilitates the collaboration between basic scientists and clinicians,” Dr. Geba said. “In one way, the great discoveries from basic science are translated into practical applications that are used in clinical and community-type research; in the other direction, the observations about human disease that are made by clinicians in their daily encounters with the patients stimulate new discoveries in basic science.”

The program’s formal curriculum includes skill-building workshops and seminars, research rotations, and a qualifying examination. Students are also encouraged to take advantage of opportunities aimed at developing skills in grant and manuscript writing, teaching, and in presenting their research. TBS students may pursue a course of study in either basic research or clinical research, but have exposure to both fields. Dr. Geba says the interdepartmental focus of the program is one of the primary reasons it is unique.

“This offers the students in the program a lot of flexibility when it comes to the project thesis they can choose,” she said. “The students in our program are allowed to have as advisors any faculty member from the University of Rochester Medical Center who is actively involved in research, and [they] can choose a project that’s placed anywhere along the entire spectrum of translational research.”

Students’ thesis committees consist of faculty members who have expertise in basic science research and those who specialize in clinical research.

“I think this is a great opportunity for the students to be in contact with experts who understand [the projects] from different perspectives,” Dr. Geba said. “In my case, I’m doing a clinical trial, so for me, it has been very helpful to have a member of my committee with a deeper understanding of the pathology of the disease.”

Mentoring and Collaboration

Dr. Geba says the greatest factor contributing to her success in the TBS program is the interaction she has with its faculty. With an emphasis on interdepartmental collaboration, the program encourages students to work with faculty members who will contribute in unique ways to their development as well-rounded scientists. Dr. Geba says she and her fellow students receive invaluable support from the leadership of the program, which includes the current program director, Dr. Patricia (P.J.) Simpson-Haidaris, and the founding program director, Dr. Nina Schor. Each student also chooses a mentor and research advisor to provide expertise and guidance throughout the research process. Dr. Thomas Pearson (Professor of Public Health Sciences; Senior Associate Dean for Clinical Research; and Director of the Clinical and Translational Science Institute) serves as both mentor and research advisor to Dr. Geba.

“The part that I enjoy the most in working with him is the balance between allowing me to work independently – to use my creative side to solve the issues that arise in [my] project – but also providing a lot of support. [He is] there as a mentor to guide me and to make sure that I move forward at a steady pace,” she said.

In addition to the support from faculty members in the TBS program, Dr. Geba says students receive assistance from individuals within the broader Medical Center community, including those affiliated with the Clinical and Translational Science Institute.

“I use extensively the Research Help Desk resources because the friendly and very knowledgeable team helped me get in contact with resources that help move the project along,” Dr. Geba said. “Another resource I find very helpful – especially for somebody in my position who is doing a clinical trial for the first time – is the Customized Action Plan, which is an online tool which assists researchers in planning and actually implementing their studies.”

Dr. Geba also reaches out to the Greater Rochester community to recruit patients for her clinical trial. She frequently interacts with clinicians associated with the Greater Rochester Practice-Based Research Network.

“I had the wonderful opportunity to present my project to the steering committee of this group twice, and I have to admit, it was an intimidating experience for a first-year student to do this,” she said. “Soon I learned that the feedback I received from the steering committee was so helpful to me.”

Falling in Love with a Terrible Disease: Type 2 Diabetes

“Type 2 diabetes is, without a doubt, one of the important health issues of the 21st century,” Dr. Geba said. “The burden of the disease is tremendous, both in terms of human suffering because of the disease complications (type 2 diabetes is a risk [factor] for cardiovascular disease and it is the main cause for blindness and non-traumatic amputations among adults) and also due to the costs related to the disease (about one tenth of the total national healthcare costs are diabetes-related).”

The statistics pertaining to diabetes are staggering. According to the American Diabetes Association, more than 25 million children and adults in the United States have diabetes, and an estimated 90-95 percent of these individuals have type 2 diabetes. Nearly 19 million people have been diagnosed with diabetes, while seven million others who have the disease are undiagnosed. Finally, an astounding 79 million people are in the pre-diabetes stage.

“It is very easy to say one quarter of the diabetics are undiagnosed, but as an absolute number, that’s seven million people who are around us who have diabetes and are not aware, don’t start treatment, are not advised to have a lifestyle change that could have such a great impact on their life,” Dr. Geba said.

According to Dr. Geba, an even more disturbing fact is that more young people are being diagnosed with type 2 diabetes.

“We used to say [when I was in medical school] that type 2 diabetes is the disease diagnosed in people 40 or over and when it’s diagnosed before that age, it’s probably type 1. That’s not the case anymore. There are children, teenagers, who are diagnosed with type 2 diabetes and, developing the disease this early in life, they also will likely develop the complications early.”

The high prevalence of undiagnosed diabetes, as well as the high prevalence of pre-diabetes, are strong incentives to continue research focused on optimizing the screening process for the disease. Currently, the tests that are used include a fasting plasma glucose test, a hemoglobin A1c test, and an oral glucose tolerance test. Dr. Geba says a necessary, yet currently absent study, is one which compares the effectiveness of these different screening strategies in a clinical setting. Such a study, which she and Dr. Pearson are now designing, would examine the cost of the tests, their convenience, and their acceptability by the patients and clinicians. Dr. Geba’s project is entitled, “Comparative effectiveness of diabetes screening strategies: a pilot study.”

“My part of the project is actually related to developing a pilot in preparation for that comparative effectiveness study,” Dr. Geba said. “We want to examine the feasibility of the recruiting strategies we plan to use in the large scale study, the feasibility of working with the clinical practices where we want to recruit our participants, and the third objective of the pilot would be to get other data that would help us plan for the sample size for the large study.”

Dr. Geba has been involved with the comparative effectiveness study since its concept phase. She is assisting with the design of the study and will be involved with its implementation – the clinical trial. It is rare that a student has the opportunity to design a clinical trial.

“Learning about all these different aspects of planning and implementing is a great opportunity for me,” she said. “Finding solutions that work in our project is sometimes challenging, but is intellectually stimulating and I think I benefit a lot from this practical experience.”

Dr. Geba explains how her personal experience with diabetes has motivated her research

Dr. Geba’s interest in studying type 2 diabetes began when she was a medical school student, and has grown deeper for personal reasons. While earning her MD, Dr. Geba initially planned to pursue a career in surgery. She often interacted with patients in the surgery clinic; many of these individuals were diagnosed with diabetes and had undergone toe amputations.

“I was moved by their suffering and I wanted to learn more about type 2 diabetes. I studied more, I became more interested, and I could honestly say I was starting to fall in love with this terrible disease. Before I knew it, I was hooked.”

Dr. Geba has also experienced type 2 diabetes on a personal level: two years ago, her mother was diagnosed with the disease. Dr. Geba says because of this, she now has a better understanding of the burden of the disease on patients and their families, as well as how important it is to educate patients in how to manage the disease.

“This personal story has a silver lining because I’m very proud of how my mother handled this – how she really cared about the advice of her primary care provider, and how she allowed us to support her during this period,” Dr. Geba said. “She did a great job; she was slightly overweight and lost a couple of pounds, she’s more careful with her diet, and she exercises more.”

Without the use of glucose-lowering drugs, Dr. Geba’s mother was able to lower her blood glucose to a normal level. Dr. Geba says this is living proof that education and lifestyle changes can make a difference in managing type 2 diabetes.

“Being in the clinic and seeing the suffering of patients – that’s such a strong motivator because you know beyond statistics, which are just numbers. It’s important to see that each of those 25 million people [with diabetes] are people who suffer; they are somebody’s mother or somebody’s spouse or somebody’s teacher or neighbor, and there is a lot of suffering. That’s a strong motivator to keep going.”

It Takes a Village to Raise a Scientist

Dr. Geba explains how the TBS program has shaped her career goals

“Being involved in this program and receiving help and advice and support from so many people with expertise in so many areas really makes me think of that old African proverb, it takes a whole village to raise a child,” Dr. Geba said. “I see [how] the involvement of so many people will help me grow as a researcher, will help me have such a well-rounded experience.”

Dr. Geba says the TBS program has changed her life. She attributes her success to the dedicated and supportive faculty members – her role models – who she says have helped shape her career path and the individual she has become. After earning her PhD, she plans to continue doing research and to pursue a career in academia, with the hopes of working as a mentor.

“I would love to give to the next generation the wonderful things that I’ve received from those ahead of me.”

Jennifer Cialone, a fourth-year medical student, says her experience with the CTSI has been instrumental in shaping her future in medicine. The TL1 Predoctoral Training Program trainee spent a year doing research on Juvenile Batten disease, and is now applying to residencies. Cialone says that by immersing herself in the opportunities of her year-out experience, she realized her passion for pediatric neurology and has been inspired to pursue a career in academic medicine.

TL1 Predoctoral Training Program

The CTSI’s TL1 Predoctoral Training Program supports medical students interested in a year-out experience of mentored research in clinical or translational science. Trainees receive a stipend, and their mentors receive funds to help support research activities. Cialone was selected for the program in 2010, between her third and fourth year of medical school. She says she was inspired to apply for the award after doing research as a Molecular and Cellular Biology major at Vanderbilt University, where she received her Bachelor of Science degree.

“I had hoped to do a year of research during medical school to get exposure specifically to clinical research because I had done bench research in undergraduate [course work],” Cialone said. “I wanted exposure to a different type of research, and so I heard about the CTSI as a potential source for funding and a good opportunity to learn more about clinical research.”

Research Focus

Cialone’s project, entitled, “A Phase II, Randomized, Placebo Controlled Trial of the Safety & Tolerability of Mycophenolate (CellCept) in Children with Juvenile Neuronal Ceroid Lipofuscinosis (JNCL),” focused on how to measure different aspects of Juvenile Batten disease in patients. Children are usually diagnosed with this neurodegenerative disease between the ages of four and eight. The disease is a very rare, recessively inherited genetic condition. From the onset to the end of the disease, children progressively lose their ability to see, move, and reason. Cialone compares the cognitive decline to dementia. Unfortunately, the disease is terminal; most patients do not survive late adolescence or young adulthood.

Cialone and her colleagues use a rating scale developed several years ago to quantify the progression of the disease.

“Since we see these kids over the years multiple times, we’ve been able to use it sort of as a natural history type of tool, and we hope to use it as an outcomes measurement for clinical trials,” Cialone said.

The main focus of Cialone’s project was to see if it would be possible to administer the tool using telemedicine. The goal is to treat patients remotely so families do not need to travel long distances to clinical sites. Cialone says the tool worked successfully this way, and that telemedicine is being used more and more frequently for clinical diagnoses.

Cialone also participated in the first controlled clinical trial for Juvenile Batten disease, which began in the summer of 2011 at the University of Rochester Medical Center. The trial will investigate whether an immunosuppressant drug called mycophenolate mofetil is safe for children with Batten disease and if it can slow or halt the progression of the disease.

Benefits of Collaboration

“Research is not really an independent, alone kind of endeavor, and I really like working with people.”

TL1 trainees work with a mentor who specializes in their field of study. Cialone’s mentor, Dr. Jonathan Mink, Chair of the Pediatric Neurology Unit, specializes in movement disorders starting in childhood. Cialone says that while working on her project, Dr. Mink allowed her to grow at her own pace and take the work where she wanted it to go.

“I actually think it’s a really great opportunity to work with people who come from all different areas, different expertise, and different viewpoints. Being in that kind of community, I think, is really enriching and exciting.”

Other members of the team also had a positive impact on Cialone’s experience. They include Dr. Erika Augustine (a pediatric neurologist and co-principal investigator of the clinical trial), Dr. Jennifer Kwon (a pediatric neurologist), Dr. Heather Adams (a pediatric neuropsychologist), Nicole Newhouse (a project coordinator), Amy Vierhile (a pediatric nurse practitioner), and Dr. Frederick Marshall (an adult neurologist and principal investigator of the clinical trial), whose expertise in dementia was critical to the work the team has done in Batten disease.

“One thing I’d love to emphasize is how important it was that I had the group of people that I worked with because Jonathan Mink and everybody were so supportive,” Cialone said. “I think working with them was a huge part of why my year was successful in any way.”

Emotional Impact

Cialone’s passion for pediatric neurology is not purely intellectual; she says spending a year working with children diagnosed with Batten disease was emotional. A first-hand look at the courage and resiliency of her young patients inspired her to want to do more to help them.

Her first exposure to the disease was at the start of her research year when she attended the Batten Disease Support and Research Association (BDSRA) conference. She participated in a support group meeting, where children, parents, and researchers talked about current research, as well as the emotional aspects of the disease.

“I think meeting those families and seeing those children, I was drawn in many ways,” Cialone said. “The families are so strong, and what they do for their kids is amazing. They are so dedicated to helping out with the research, even if it might not help their child, help another one, which is very humbling.”

Cialone says she is amazed by the courage of the parents and the resiliency of the children.

“There’s one family with two sons [who are diagnosed with Batten disease] that I’ve met further along in their teenage years – which is further along into the disease – and they are impaired in a lot of ways that kids [with Batten disease] are impaired, but they have so much joy in so many of the things that they do,” she said. “There’s a video of the older boy – he’s part of the baseball team his dad coaches – and he got to hit one of the balls and run around the bases, and it was amazing to see.”

She says the most recent conference she attended was particularly emotional because she had spent the year learning about the disease and working closely with the children.
“Seeing a lot of the kids that were at the beginning of the disease and seeing the kids at the end of the disease, I think had a much more profound effect on me, but it also made me want to continue this because there’s so much more to do for the disease.”

Opportunities with the CTSI

In addition to the BDSRA conference, Cialone was able to attend other research conferences with the support of the CTSI. She says she especially values her experience at the 2011 Clinical and Translational Research and Education Meeting in Washington, D.C. because she was exposed to research in many different fields, not just pediatric neurology.

“It was unlike any of the conferences I had been to before, which had all been very focused on one area of medicine,” Cialone said. “It was neat because when I went and presented my poster, I got to talk to people who were from all different fields.”

She also stressed how valuable she found the experience of actually doing the research.
“I got a chance to explore research in a way that I had not done before – from working with a team to develop a project or understand how you work through questions in a research project, to analyzing data, [learning] more about statistics than I’d ever known before, and all the way through presenting posters and publishing papers.”
Cialone says she appreciated the talks and seminars sponsored by the CTSI, as well as the freedom to choose which to attend.

“I attended some of the lectures and I found them very helpful, but there were some that I wasn’t as interested in, so I was able to take that time and work on my project or go to clinic and see child neurology from a different aspect,” she said. “I was able to make the year what I wanted it to be, as opposed to following another structured schedule, and that, actually, I think is really important in making me more productive.”

Impact on Her Future

Cialone says participating in the TL1 Program helped her focus her future ambitions. After being exposed to both the clinical and research sides of the field, she realized she would like to blend seeing patients with doing research and teaching. Therefore, she is now pursuing a career in academic medicine. Working with her colleagues and seeing what their lives are like helped her realize that such a career is fulfilling and would make her happy.

“I think this experience with CTSI is absolutely a huge reason for why I’m going into this residency and why I have these ideals of academic medicine because I found that it was very do-able,” she said.

Currently, Cialone is interviewing for residency positions in pediatric neurology. The program is a combination of pediatrics training (two years) and neurology training (three years). Cialone says before participating in the TL1 Program, she knew she had an interest in pediatric neurology (she was exposed to the field during her second-year neuroscience course, and also during her third-year clerkships), but she wasn’t ready to commit to it for residency.

“It’s a pretty big commitment for the five-year program, and so having the chance to do research exposed me to research and let me know that academic medicine is really an interest of mine,” she said. “[Participating in the TL1 Program] was one of the best decisions I’ve made. It was amazing.”

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Tim Bushnell, PhD

-Director, URMC Shared Resources Laboratories

As the Director of URMC’s Shared Resource Laboratories, Tim Bushnell, PhD, serves as an ambassador for building the bridge between basic science research facilities and clinical scientists in order to drive clinical and translational research at the University of Rochester. The tools housed by the Shared Resource Laboratories give investigators at the University, as well as throughout New York State, the ability to conduct studies geared toward personalized medicine. When speaking of the Labs, Dr. Bushnell paraphrases an old BASF commercial, “We don’t make the science, we help make it better.”

What are Shared Resource Laboratories?

The Shared Resource Laboratories consist of a series of technologies, resources, and staff members that support investigators with their research. High-end tools, including the laser capture microdissection instrument in the Confocal and Conventional Microscopy Core; the Hi-Seq 2500 in the Rochester Genomics Center; and an analytical flow cytometer, image stream, cell sorters, and a CyTOF in the Flow Cytometry Core are used by hundreds of investigators every day.

“The shared resources represent the bridge between the questions that researchers are asking and the end product – be it a paper, be it a patent, be it something that improves the human condition,” Dr. Bushnell said. “We provide that scientific technical expertise because it’s very difficult for one researcher to be an expert in all the different tools.”

The Shared Resource Laboratories are made up of more than 20 facilities which house a variety of state-of-the-art instruments. Several of the more popular facilities include:

Confocal and Conventional Microscopy Core

The Confocal and Conventional Microscopy Core assists researchers in attaining high quality imaging data through advanced microscopy instruments. The laser capture microdissection instrument, for instance, allows researchers to outline an individual cell in a sample, remove the cell from the sample using a UV laser, and process the cell for RNA, DNA, or proteomic profiles. The instrument can identify tissue using bright field microscopy or florescence microscopy.

Dr. Linda Callahan, Director of the Confocal and Conventional Microscopy Core, says investigators use the instrument to understand where cells are within affected tissue.

“[We can] dissect out different cell types from different tissues so we know exactly what the profiles are,” she said.

Rochester Genomics Research Center

The Rochester Genomics Research Center supports all aspects of genomics research at the University of Rochester, including studies in viral genome, HIV, microbiome, and general RNA expression. The Illumina Hi-Seq 2500 generates millions of sequenced data points that researchers can map to a human reference genome. Comparing this genome to disease-specific mutations and gene abnormalities is effective in the diagnosis and treatment of disease.

“What once took years and millions and millions of dollars to sequence the entire human genome, we can now get down to about five days and [a] cost of only about $1,000,” said Dr. John Ashton, Associate Director of the Genomics Research Center. “This is extremely powerful for research, as well as for personalized medicine.”

Flow Cytometry Core

The Flow Cytometry Core is a full-service facility offering a range of top-of-the-line digital flow cytometers, an image stream, cell sorters, and a CyTOF mass cytometer.

The analytical flow cytometer measures the physical and biochemical characteristics of cells both on the surface of cells and intercellularly.

“It’s important in clinical research, it’s important in clinical diagnostic work, it’s important in basic research,” Dr. Bushnell said. “Our tools are geared toward helping investigators identify the unique populations in a single cell suspension, be it from blood or bone marrow or tissue culture or any other sample we can put in a single cell.”

Cells identified by an analytical flow cytometer are represented as dots on a plot. In 1979, University of Rochester investigator Leon Wheeless published a paper that sought to combine the principles of flow cytometry with the ability to image and visualize the entire cell and its processes. The technical limitations of the time prevented the project from moving forward, but in the late 2000’s, Amnis, a company specializing in flow cytometry, made the idea possible when it released the Amnis Image Stream. The University acquired the instrument in 2006.

The technology of the analytical flow cytometer was combined with the technology developed to make inkjet printers to create a cell sorter: a tool that separates and purifies cells based on their surface characteristics. The cells moving through the sorter appear to be a solid stream, but they are actually a series of droplets. The cells can then be returned to the researcher at 99% purity for use in downstream work (culture, genomics, proteomics, etc.).

The Flow Cytometry Core is also home to the CyTOF, an instrument that combines the principles of flow cytometry with a detector from a mass spectrometer. This hybrid tool measures highly dimensional data to screen and characterize detailed intercellular pathways. URMC’s CyTOF was the seventh installed at a research institution in the United States. URMC acquired the instrument through a partnership within the UNYTE Translational Research Network and it is supported by an NIH shared instrumentation grant.

How can researchers access the services?

To schedule an initial consultation, investigators can call or e-mail the directors of the core facilities. During the consultation, the directors describe the correct tools investigators can use for their research, and the best practices for doing their experiments. Researchers are assisted through every step of the process, including sample preparation, utilizing the instruments to analyze the samples, interpreting the data, and then transforming the outcomes into a publishable form.

How much do the services cost?

“We drive the cost as low as possible for each investigator,” Dr. Bushnell says.

Rates for the services, which are subsidized by the University, are calculated based on cost recovery. Since individual resources have different pricing structures, Dr. Bushnell recommends investigators contact the core directors or visit the Shared Resources website.

Where can researchers find more information?

To learn more about the Shared Resource Laboratories and to contact the core directors, click here. Investigators can also contact Dr. Bushnell directly via e-mail or by phone, at 585-273-5535

Click here for a video of Dr. Bushnell explaining the purpose of and how to use the Shared Resource Laboratories.

Dr. Robert Block, Assistant Professor in the Epidemiology Division of the Department of Public Health Sciences, is a prime example of how researchers and clinicians can use a variety of CTSI funding opportunities to move their projects forward. Dr. Block is a 2008 Novel Methodologies Awardee (Project: “Potent Lipid Mediator Measurement Methodology,” with Dr. Steve Georas), a 2007 KL2 Scholar (Project: “The Role of Fatty Acids and their Metabolites in the Pathophysiology of Sudden Cardiac Death”), a 2007 UNYTE Pilot Funding Awardee (Project: “Potent Lipid Mediators and Ischemic Heart Disease,” with Dr. Shaker Mousa and Dr. Thomas Brenna), and a 2006 Laboratory Support Center Awardee (Project: “15-Epi-lipoxin in Ischemic Cardiomyopathy”). Dr. Block says the funding support he has received from the CTSI and UNYTE has made much of his research possible.

A preventive cardiologist, Dr. Block specializes in the care of patients with hyperlipidemia, or high blood cholesterol levels. His expertise includes the diagnosis and treatment of patients with complex lipid disorders and familial cholesterol diseases. His research focuses on how nutrition affects the risk of cardiovascular disease, especially how fatty acids and their metabolites can impact heart disease risk (particularly in patients with coronary artery disease).

Involvement with the CTSI and UNYTE

Dr. Block’s interest in translational research was fostered under the guidance of his mentor, Dr. Thomas Pearson, Director of the CTSI. Dr. Block has also partnered with researchers from other institutions through the UNYTE Translational Research Network. UNYTE, a component of the CTSI, serves as a national model of research collaboration and includes 17 of the region’s premier biomedical research institutions. Dr. Block became its Managing Co-Director in 2010. He says UNYTE’s impact on medical community is invaluable.

“It helps people’s health more for the amount of resources expended – financial and otherwise,” he said. “It brings people together from different backgrounds, different skill sets, different hypotheses, and different areas of focus, and these help to bring people together so they can think about what’s really important.”

Dr. Block says, as a clinician, it is beneficial for him to work with individuals who have different areas of focus; he says biochemists and laboratory scientists offer unique points of view, which are essential in recognizing the true value and impact of his research.

“Much of the time, it simply takes a team approach to think differently about things and to make adequate use of other people’s expertise,” he said.

He also stressed the value of UNYTE for students, trainees, and young faculty members.

“I think [UNYTE] is a great opportunity for them because it will make their time spent doing research much more efficient. I think they’ll have a greatly enhanced ability to get funding to do the kind of research they want to do.”

Research Focus

Dr. Block received support through a UNYTE collaborative award with Shaker Mousa, PhD, at the Albany College of Pharmacy, and Thomas Brenna, PhD, at Cornell University. The project, which began in 2007, investigated how fatty acids and their metabolites affect cardiovascular disease through angiogenesis, or the development of new blood vessels. Dr. Block and his colleagues found that some fatty acid metabolites increase angiogenesis.

“Even though it sounds like a great thing to have new blood vessels in your heart, for example, it turns out that much of the data supports angiogenesis to be a problem in increasing the risk of heart attack and stroke,” Dr. Block said.

In addition to this study, Dr. Block is also investigating aspirin resistance in patients with diabetes. Aspirin helps prevent cardiovascular disease, but because diabetics do not have a normal response to aspirin, they do not experience its beneficial effects. As a result, they are at high risk for heart attack and stroke. Dr. Block is again collaborating with Dr. Mousa and Dr. Brenna to determine if fish oil enhances the effects of aspirin. This study is funded through an R21 from the NIH. It utilizes the URMC Clinical Research Center and is expected to be completed by the end of May 2011.Click here for a video of Dr. Block explaining aspirin resistance in diabetes patients

Dr. Block is also investigating the role omega-3 fatty acids (particularly docosahexaenoic acid, or DHA) have on weight loss. He says there are a few small studies that suggest people may lose weight when they eat more fish. There is also data showing that DHA has effects on something like serotonin in the brain, which regulates people’s appetites. Therefore, DHA could contribute to how people perceive food and how they determine what they want to eat. Dr. Block says this is a new way of thinking, but it is something he plans to explore.

How will this research impact people’s every day heart health? Dr. Block says although people often think that how much they eat is the most important indicator of their wellbeing, he has discovered that what people eat and how the body processes it is more telling. Dr. Block is now exploring new therapies based on the fatty acids people ingest, as well as medications used in preventive cardiology, to determine how they affect fatty acid metabolism.

With blood vessel disease currently the number one cause of death in the United States and the world, Dr. Block says the long term goal of his studies is to reduce people’s risk for these diseases, and to improve the prognosis for patients who have already been diagnosed.

Why are You Drawn to This Type of Research?

Dr. Block says in today’s world of expensive medications, it would be ideal to rely on a behavioral area of focus when treating certain conditions. Therapies based on what people eat and how much they exercise would eliminate excessive reliance on medications, which often have side effects. He is working with Dr. Geoffrey Williams in the Center for Community Health to try to improve people’s lifestyle factors, with the goal of lowering cholesterol and reducing the risk of cardiovascular disease.

“If we can use some really simplistic, inexpensive ways to improve people’s health, that’s what I’m shooting for.”